{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361699994334271744.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1152/ajpendo.00755.2009"}},{"identifier":{"@type":"URI","@value":"https://www.physiology.org/doi/pdf/10.1152/ajpendo.00755.2009"}}],"dc:title":[{"@value":"PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>The peroxisome proliferator-activated receptor-γ (PPARγ) coactivator-1α (PGC-1α) is a major regulator of exercise-induced phenotypic adaptation and substrate utilization. We provide an overview of 1) the role of PGC-1α in exercise-mediated muscle adaptation and 2) the possible insulin-sensitizing role of PGC-1α. To these ends, the following questions are addressed. 1) How is PGC-1α regulated, 2) what adaptations are indeed dependent on PGC-1α action, 3) is PGC-1α altered in insulin resistance, and 4) are PGC-1α-knockout and -transgenic mice suitable models for examining therapeutic potential of this coactivator? In skeletal muscle, an orchestrated signaling network, including Ca<jats:sup>2+</jats:sup>-dependent pathways, reactive oxygen species (ROS), nitric oxide (NO), AMP-dependent protein kinase (AMPK), and p38 MAPK, is involved in the control of contractile protein expression, angiogenesis, mitochondrial biogenesis, and other adaptations. However, the p38γ MAPK/PGC-1α regulatory axis has been confirmed to be required for exercise-induced angiogenesis and mitochondrial biogenesis but not for fiber type transformation. With respect to a potential insulin-sensitizing role of PGC-1α, human studies on type 2 diabetes suggest that PGC-1α and its target genes are only modestly downregulated (≤34%). However, studies in PGC-1α-knockout or PGC-1α-transgenic mice have provided unexpected anomalies, which appear to suggest that PGC-1α does not have an insulin-sensitizing role. In contrast, a modest (∼25%) upregulation of PGC-1α, within physiological limits, does improve mitochondrial biogenesis, fatty acid oxidation, and insulin sensitivity in healthy and insulin-resistant skeletal muscle. Taken altogether, there is substantial evidence that the p38γ MAPK-PGC-1α regulatory axis is critical for exercise-induced metabolic adaptations in skeletal muscle, and strategies that upregulate PGC-1α, within physiological limits, have revealed its insulin-sensitizing effects.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381699994334271744","@type":"Researcher","foaf:name":[{"@value":"Vitor A. Lira"}],"jpcoar:affiliationName":[{"@value":"Center for Skeletal Muscle Research, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699994334271617","@type":"Researcher","foaf:name":[{"@value":"Carley R. Benton"}],"jpcoar:affiliationName":[{"@value":"Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699994334271616","@type":"Researcher","foaf:name":[{"@value":"Zhen Yan"}],"jpcoar:affiliationName":[{"@value":"Center for Skeletal Muscle Research, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699994334271618","@type":"Researcher","foaf:name":[{"@value":"Arend Bonen"}],"jpcoar:affiliationName":[{"@value":"Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"01931849"},{"@type":"EISSN","@value":"15221555"}],"prism:publicationName":[{"@value":"American Journal of Physiology-Endocrinology and Metabolism"}],"dc:publisher":[{"@value":"American Physiological Society"}],"prism:publicationDate":"2010-08","prism:volume":"299","prism:number":"2","prism:startingPage":"E145","prism:endingPage":"E161"},"reviewed":"false","url":[{"@id":"https://www.physiology.org/doi/pdf/10.1152/ajpendo.00755.2009"}],"createdAt":"2010-04-07","modifiedAt":"2021-10-25","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050857899426014336","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Methylglyoxal reduces molecular responsiveness to 4 weeks of endurance exercise in mouse plantaris muscle"}]},{"@id":"https://cir.nii.ac.jp/crid/1360002216828943744","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Coenzyme Q10 Improves Lipid Metabolism and Ameliorates Obesity by Regulating CaMKII-Mediated PDE4 Inhibition"}]},{"@id":"https://cir.nii.ac.jp/crid/1360002217477039488","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Oxygen Consumption and Usage During Physical Exercise: The Balance Between Oxidative Stress and ROS-Dependent Adaptive Signaling"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004237733296896","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"CD36 is essential for endurance improvement, changes in whole-body metabolism, and efficient PPAR-related transcriptional responses in the muscle with exercise training"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285708465807104","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"MiR-494-3p regulates mitochondrial biogenesis and thermogenesis through PGC1-α signalling in beige adipocytes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360290617529577344","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Mitochondrial Dysfunction in Kidney Disease and Uremic Sarcopenia"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565168505104512","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"High-intensity interval training increases intrinsic rates of mitochondrial fatty acid oxidation in rat red and white skeletal muscle"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567183444182656","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Loss of microRNA-23–27–24 clusters in skeletal muscle is not influential in skeletal muscle development and exercise-induced muscle adaptation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360583650977577728","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Peroxisome proliferator-activated receptor γ coactivator 1α regulates downstream of tyrosine kinase-7 (Dok-7) expression important for neuromuscular junction formation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846644347434112","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Transcutaneous Application of Carbon Dioxide (CO2) Induces Mitochondrial Apoptosis in Human Malignant Fibrous Histiocytoma In Vivo"}]},{"@id":"https://cir.nii.ac.jp/crid/1360853567517705088","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Chronic exercise training activates histone turnover in mouse skeletal muscle fibers"}]},{"@id":"https://cir.nii.ac.jp/crid/1360853567617031680","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Integrin-Ligand Interactions in Inflammation, Cancer, and Metabolic Disease: Insights Into the Multifaceted Roles of an Emerging Ligand Irisin"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865815678627968","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Physical inactivity induces insulin resistance in plantaris muscle through protein tyrosine phosphatase 1B activation in mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1361975846188086784","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Effect of a single bout of exercise on clock gene expression in human leukocyte"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001205415899392","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Effect of exercise on HIF-1 and VEGF signaling"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001205416887936","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Monocarboxylate transporter and lactate metabolism"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001206301157632","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Endurance exercise ameliorates low birthweight developed catch-up growth related metabolic dysfunctions in a mouse model"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679899358592","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"骨格筋の恒常性維持に関する最新知見"},{"@language":"en","@value":"New insight in skeletal muscle homeostasis"},{"@value":"教育講座 骨格筋の恒常性維持に関する最新知見"},{"@language":"ja-Kana","@value":"キョウイク コウザ コッカクキン ノ コウジョウセイ イジ ニ カンスル サイシン チケン"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282680391297280","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"High-intensity interval training enhances oxidative capacity and substrate availability in skeletal muscle"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282680392126464","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Reactive oxygen species and endurance training-induced adaptations"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282680392979456","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Molecular signaling mechanisms that mediate exercise training effects on insulin sensitivity"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282681303175808","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Inhibition of Oxidative Stress by Antioxidant Supplementation Does Not Limit Muscle Mitochondrial Biogenesis or Endurance Capacity in Rats"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1152/ajpendo.00755.2009"},{"@type":"CROSSREF","@value":"10.1038/s41598-017-08899-7_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.1089/ars.2011.4498_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.14814/phy2.13282_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.7600/jpfsm.1.5_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.7600/jspfsm.67.245_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.1038/s41598-018-33438-3_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.3389/fphys.2020.565023_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.1139/apnm-2012-0257_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.1038/s41598-018-37765-3_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.7600/jpfsm.1.247_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.7600/jpfsm.2.117_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.1152/japplphysiol.00539.2021_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.1038/s41598-024-52198-x_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.1371/journal.pone.0049189_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.3177/jnsv.63.277_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.1096/fj.202002027rr_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.3389/fcell.2020.588066_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.3389/fphys.2023.1198390_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.7600/jpfsm.5.13_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.1507/endocrj.ej15-0479_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.7600/jpfsm.2.463_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"},{"@type":"CROSSREF","@value":"10.1152/japplphysiol.00891.2019_references_DOI_1tcnqWxWaXajKWnuts2Au6XXigf"}]}